Publications by authors named "Hung-Hsueh Chou"

87 Publications

Postoperative adjuvant dose-dense chemotherapy with bevacizumab and maintenance bevacizumab after neoadjuvant chemotherapy for advanced ovarian cancer: A phase II AGOG/TGOG trial.

Eur J Obstet Gynecol Reprod Biol 2021 Apr 18;262:13-20. Epub 2021 Apr 18.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University, Taoyuan, Taiwan. Electronic address:

Objective: The objective of this study is to evaluate the safety and efficacy of adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer.

Study Design: This phase II clinical trial using Simon's minimax two-stage design was conducted. At the first stage, 13 subjects were enrolled, and the trial would proceed to second stage if ≤3 subjects discontinued treatment for study-defined significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and primary peritoneal cancer deemed not feasible for primary cytoreductive surgery were enrolled after 3-4 cycles of NAC and IDS without disease progression. NAC could be either weekly paclitaxel (80 mg/m) (dose-dense) plus 3-weekly carboplatin (AUC5-6) or 3-weekly conventional schedule. After IDS, postoperative dose-dense adjuvant chemotherapy for 3 cycles at least (best to 6 cycles), and 3-weekly bevacizumab 15 mg/kg was given since postoperative cycle 2. Further 3-weekly maintenance bevacizumab 15 mg/kg was given intravenously for 17 cycles.

Results: Of the 22 enrolled subjects, 13 (59.1 %) had no gross lesion after IDS. Of the 13 subjects enrolled on the 1 st stage, one study-defined significant AE occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median progression-free survival (PFS) was 22.1 months (95 % confidence interval [CI], 13.7-30.5), and the median overall survival (OS) was 49.2 months (95 % CI, 33.8-64.6). Peritoneal Cancer Index score at entering abdomen during IDS was significant for PFS (>12 vs ≤ 12: p = 0.003). One of the 22 subjects did not receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs included thrombocytopenia of 38.1 %, neutropenia 71.4 %, and anemia 28.6 %. Study-defined significant AEs of bowel perforation, poor-healing wound, and hypertension were found in 1 case each, respectively.

Conclusion: This phase II trial demonstrated adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after NAC was feasible with tolerable toxicity and comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase or dose-dense scheduling throughout.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2021.04.017DOI Listing
April 2021

Redefining the Reconstructive Ladder in Vulvoperineal Reconstruction: The Role of Pedicled Perforator Flaps.

J Reconstr Microsurg 2021 Apr 14. Epub 2021 Apr 14.

Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.

Background:  Gynecological reconstruction is difficult, particularly in cases with recurrence and received previous surgeries and/or radiotherapy and necessitate secondary reconstruction. Perforator flaps can preserve other donor sites for potential later reconstruction, and they also can be better tailored to the defect. We hypothesized that the use of perforator-based flaps can better restore the defect with less complications.

Methods:  A retrospective review was conducted of all patients who underwent vulvar-perineum reconstruction between 2011 and 2018 by the senior author, and oncologic and reconstructive outcomes and complications were analyzed.

Results:  Thirty-three patients underwent 55 soft tissue reconstructions for vulvar-perineum defects during the study period. The mean follow-up time was 27.6 ± 28.9 months. Squamous cell carcinoma was the most common cancer (45.5%). For 11 patients (33.3%), the procedures were performed for the treatment of recurrent cancer. The average defect size was 39.8 ± 34.3 cm. The overall survival rate was 90.3%. Profunda artery perforator flaps were the most commonly applied flap for reconstruction in both the primary and recurrent groups. Poor wound healing was the most common complication which occurred in 10 of the 55 flaps (18.2%). Perforator flaps presented fewer complications than myocutaneous flaps or traditional random flaps. Similarly, Island pedicle flap design also presented fewer complications than traditional rotation flaps. With proper reconstruction, previous surgery or radiotherapy did not contribute to an increase in complications.

Conclusion:  In our experience, perforator flaps can provide satisfactory reconstruction for perineum reconstruction with low postoperative complications while preserving other donor sites in the event of disease recurrence for repeat resection and reconstruction. Previous surgery or radiotherapy did not increase the complications or preclude its usage. A redefined reconstructive ladder was created to help selecting the best state-of-the-art technique for reconstruction to achieve better results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1727199DOI Listing
April 2021

Molecular evidence for a clonal relationship between synchronous uterine endometrioid carcinoma and ovarian clear cell carcinoma: a new example of "precursor escape"?

J Mol Med (Berl) 2021 Mar 25. Epub 2021 Mar 25.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center and Chang Gung University College of Medicine, 5 Fushin St., Guishan, Taoyuan, 333, Taiwan.

Synchronous endometrial and ovarian carcinomas (SEOCs) that share the same endometrioid histology are generally considered as the result of metastatic spread from one organ to another. However, SEOCs with different histologies are regarded as distinct primary lesions that arise independently from each other. This study was undertaken to compare the mutational landscape of SEOCs with different histologies to confirm or refute the hypothesis of an independent origin. Four patients with synchronous uterine endometrioid carcinoma (UEMC) and ovarian clear cell carcinoma (OCCC) were examined. UEMCs were accompanied by endometrial hyperplasia/endometrioid intraepithelial neoplasia, whereas endometriosis was evident in two cases. Paired UEMC and OCCC specimens were subjected to mutation analysis with massively parallel sequencing. Surprisingly, we found that 50% (2/4) of paired SEOCs with different histologies shared the same somatic mutations, some of which localized in cancer driver genes. Clonality analyses indicated that these tumors were clonally related to each other. Notably, 75% (3/4) of the study patients had Lynch syndrome. The cancer-specific survival figures of patients with synchronous UEMCs and OCCCs were more favorable than those observed in a historical cohort of patients with isolated stage 2/3 OCCCs. Taken together, we set forth a potential explanation that considers clonally related SEOCs as a result of "precursor escape" - whereby precursor cells of endometrial cancer spread beyond the uterus to reach the pelvis and eventually evolve into an OCCC under an increasing mutational burden. KEY MESSAGES: • SEOCs characterized by different histologies are rare. • All cases of SEOCs were accompanied by endometrial hyperplasia. • Fifty percent of SEOCs were clonally related to each other. • Shared mutations in cancer driver genes were evident among SEOCs. • Clonally related SEOCs may be a result of "precursor escape." • Lynch syndrome is highly prevalent in patients with UEMC and synchronous OCCC. • The prognosis of synchronous UEMC and OCCC was favorable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00109-021-02064-4DOI Listing
March 2021

Role of human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia.

Int J Cancer 2021 Feb 1;148(3):665-672. Epub 2020 Sep 1.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Branch and Chang Gung University, Taoyuan, Taiwan.

Human papillomavirus (HPV) is the well-established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high-grade cervical intraepithelial neoplasia (HG-CIN). We conducted an observational study for long-term outcomes and HPV genotype changes after conization for HG-CIN. Between 2008 and 2014, patients with newly diagnosed HG-CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG-CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non-surveillance (non-S) group. For the S group (n = 493), the median follow-up period was 74.3 months. Eighty-four cases had recurrent CIN Grade 2 or worse (CIN2+) (5-year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type-specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9-valent vaccine types. Among the 7397 non-S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non-S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type-specific HPV infections, effective therapeutic vaccines are an unmet medical need.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.33251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754315PMC
February 2021

Comprehensive genomic profiling reveals ubiquitous KRAS mutations and frequent PIK3CA mutations in ovarian seromucinous borderline tumor.

Mod Pathol 2020 12 2;33(12):2534-2543. Epub 2020 Jul 2.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Linkou Medical Center, Taoyuan, Taiwan.

The molecular underpinnings of seromucinous borderline tumor (SMBT) - an uncommon ovarian epithelial neoplasm characterized by association with endometriosis, frequent bilateral ovarian involvement, and occasional progression to invasive carcinoma - remain poorly understood. Here, we sought to comprehensively characterize the mutational landscape of SMBT and elucidate the clonal relationship between bilateral ovarian SMBTs. We also compared the mutational profiles between SMBTs and concurrent invasive carcinomas. Formalin-fixed, paraffin-embedded tissue specimens were retrieved from 28 patients diagnosed with SMBT. Massively parallel sequencing of 409 cancer-related genes was conducted to identify somatic mutations in 33 SMBT samples and four concurrent invasive carcinoma specimens. TERT promoter mutations were assessed by Sanger sequencing, whereas immunohistochemistry was used as a surrogate tool for detecting deletions or epigenetic silencing of relevant tumor suppressor genes. Twenty-six (92.9%) of the 28 patients were diagnosed with stage I SMBTs. Seven (25%) cases showed bilateral ovarian involvement and 13 (46%) had concomitant endometriosis. Concurrent ovarian carcinomas were identified in three patients, whereas one case had a synchronous endometrial carcinoma. Somatic mutations in the KRAS, PIK3CA, and ARID1A genes were identified in 100, 60.7, and 14.3% of SMBT samples, respectively. In contrast, TERT promoter mutations and DNA mismatch repair deficiencies were absent. Sequencing of paired specimens from patients with bilateral SMBT revealed the presence of at least two shared somatic mutations, suggestive of a clonal relationship. Similarly, we identified shared somatic mutations between SMBT samples and concurrent ovarian carcinoma specimens. Taken together, these findings demonstrated a distinct mutational landscape of SMBT in which (1) KRAS is invariably mutated, (2) PIK3CA is frequently mutated, and (3) TERT promoter mutations and DNA mismatch repair deficiencies are absent. Our findings represent the first extensive characterization of this rare ovarian neoplasm, with potential implications for disease classification and molecular diagnostics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-020-0611-3DOI Listing
December 2020

Amniotic Fluid Stem Cells Improve Rat Bladder Dysfunction After Pelvic Nerve Transection.

Cell Transplant 2020 Jan-Dec;29:963689720909387

College of Medicine, Chang Gung University, Taoyuan.

The effects of human amniotic fluid stem cells (hAFSCs) transplantation on bladder dysfunction after pelvic nerve transection (PNT) remain to be clarified. Five groups of female Sprague-Dawley rats were studied including sham operation, unilateral PNT alone or plus hAFSCs transplantation, and bilateral PNT alone or plus hAFSCs transplantation. hAFSCs were injected at the site of PNT. Cystometries, neurofilament density within bladder nerves, and the expressions of bladder protein gene-product 9.5 (PGP9.5), growth-associated protein 43 (GAP-43), nerve growth factor (NGF), p75 (NGF receptor), CXCL12, CCL7, and enkephalin were studied. Compared to sham-operation group, bladder weight increased and neurofilament density decreased at 10 and 28 days after unilateral and bilateral PNT, but all improved after hAFSCs transplantation. Unilateral PNT could increase bladder capacity, residual volume, and number of nonvoiding contractions but decrease peak voiding pressure and leak point pressure. Bilateral PNT caused overflow incontinence and increased the number of nonvoiding contractions. These cystometric parameters improved after hAFSCs transplantation. After PNT, bladder PGP9.5 mRNA and immunoreactivities decreased at 10 and 28 days, GAP-43 mRNA and immunoreactivities increased at 10 days and decreased at 28 days, both NGF and p75 mRNAs and immunoreactivities increased at 10 and/or 28 days, and enkephalin immunoreactivities decreased at 10 and 28 days, but these were all improved after hAFSCs transplantation. Our results showed that bladder dysfunction induced by PNT could be improved by hAFSCs transplantation, and PGP9.5, GAP-43, and neurotrophins could be involved in the mechanisms of nerve regeneration after hAFSCs transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0963689720909387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444231PMC
June 2021

Dose-dense chemotherapy with weekly paclitaxel and 3-weekly carboplatin for recurrent ovarian cancer.

Taiwan J Obstet Gynecol 2020 Jan;59(1):21-27

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, Taiwan; Chang Gung University, College of Medicine, Taiwan. Electronic address:

Objective: To analyze the response to dose-dense chemotherapy of weekly paclitaxel and 3-weekly carboplatin in recurrent ovarian cancer, and to report results of literature review.

Materials And Methods: Patients accepted weekly paclitaxel 80 mg/m on day 1, 8, 15 and carboplatin on day1 at area under curve (AUC) 6 every 21 days were reviewed for the response rate, progression-free survival, overall survival, and toxicity during January 2012 to April 2016 in Chang Gung Memorial Hospital at Linkou, Taiwan.

Results: Sixteen patients with recurrent ovarian cancer, including 1 platinum-resistant, 7 partially platinum-sensitive, and 8 platinum-sensitive, accepted a median of 6 cycles of chemotherapy (range 3-10). The overall response rate (ORR) and complete response (CR) rate were 93.8%, and 62.5%, respectively. The median PFS of all patients were 10.9 months (range 4.3-40.5). The median time to response (TTR) was 29.0 days (range 19.6-38.4). The median disease-free survival (DFS) after CR was 5.6 months (range 1.2-34.2). Grade 3 at least toxicity included anemia (6.3%), neutropenia (50%), and thrombocytopenia (18.8%). Twenty-nine articles on phase I, II, III, or retrospective studies of dose-dense chemotherapy with weekly paclitaxel were reviewed.

Conclusion: This is the first report using Japanese Gynecologic Oncology Group 3016 protocol, weekly paclitaxel and 3-weely carboplatin, on recurrent ovarian cancer. The current study showed high ORR and CR with tolerable toxicities. Our study suggested dose-dense chemotherapy with paclitaxel, especially combining carboplatin created high efficacy probably by anti-angiogenesis. However, consolidation or maintenance therapy is needed to prolong DFS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tjog.2019.10.003DOI Listing
January 2020

mutation status in patients with metachronous breast and ovarian malignancies: clues towards the implementation of genetic counseling.

J Gynecol Oncol 2020 May 25;31(3):e24. Epub 2019 Oct 25.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center and Chang Gung University, College of Medicine, Taoyuan, Taiwan.

Objective: The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by mutation analysis in hospital-based cases.

Methods: We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify mutations and large genomic rearrangements, respectively. When mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members.

Results: A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in and 2 in ). All mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were mutation carriers. All of them had family members with -associated malignancies.

Conclusions: Our results provide pilot evidence that mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3802/jgo.2020.31.e24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189074PMC
May 2020

Management and clinical outcomes of patients with recurrent/progressive ovarian clear cell carcinoma.

J Formos Med Assoc 2020 Apr 6;119(4):793-804. Epub 2019 Dec 6.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address:

Background/purpose: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients.

Methods: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or progression after primary treatment were analyzed. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS).

Results: A total of 64 patients experienced treatment failure (49 recurred after remission and 15 progressed without remission). The 5-year CSS rates of recurrent/progressive OCCC patients were 22.9% (progression group: median CSS 5.9 months [range, 0.8-25.2] vs recurrence group: 43.6 months [range, 7.1-217.8]; p < 0.001). Patients with solitary recurrence had significantly better SAR than those with disseminated relapse (median: not reached vs 10.4 months, p < 0.001). On multivariate analysis, six models each for SAR and CSS were formulated alternatively including highly correlated variables for the recurrence group. Of these models, solitary relapse pattern (HR: 0.07, p < 0.001), progression-free interval (PFI) > 12 months (HR: 0.22-0.40, p = 0.001 and p = 0.023), CA125 < 35 U/mL at initial recurrence (HR: 0.32, p = 0.007), and overall salvage treatment including radiotherapy (HR: 0.19, p = 0.001) were significant predictors of favorable SAR. The same significant predictors were selected for CSS.

Conclusion: Recurrent OCCC can be treated with curative intent if the relapse is solitary and can be completely resected or encompassed with radiotherapy, whereas novel therapies are needed for disseminated relapse or progression during primary treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2019.11.018DOI Listing
April 2020

Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group.

J Gynecol Oncol 2020 Jan 26;31(1):e5. Epub 2019 Jul 26.

Data Management and Biostatistical Core, Asian Gynecologic Oncology Group, Taoyuan, Taiwan.

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer.

Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m², n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence /homologous recombination deficiency (HRD) genes, because /HRD mutations (/HRD) are known to be associated with better prognosis.

Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of or /HRD was not significantly biased between the two arms. Wild-type /non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11-1.18; p=0.091).

Conclusions: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3802/jgo.2020.31.e5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918895PMC
January 2020

Detecting recurrent ovarian cancer: revisit the values of whole-body CT and serum CA 125 levels.

Acta Radiol 2019 Oct 24;60(10):1360-1366. Epub 2019 Jan 24.

Department of Medical Imaging and Intervention, Imaging Core Lab, Institute for Radiological Research, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0284185118822649DOI Listing
October 2019

Effectiveness and appropriateness in the application of office hysteroscopy.

J Formos Med Assoc 2019 Nov 2;118(11):1480-1487. Epub 2019 Jan 2.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital (Linkou), Tao-Yuan, Taiwan; Chang Gung University College of Medicine, Tao-Yuan, Taiwan.

With the advances in miniature instruments, office hysteroscopy on conscious patients has been the standard to explore the intrauterine pathology, with the ability to perform some minor procedures concomitantly. Patients usually appreciate the efficient "see and treat" procedures with such minimal discomfort that exempt from the inconvenience of going into the operating room and the need for anesthesia. However, controversies exist in the appropriateness of its application in some clinical situations. Concerns include (1) the criteria for hysteroscopy applied in the vast number of patients suffering from abnormal uterine bleeding or subfertility, and (2) the frequency for repeated hysteroscopy on some kinds of patients, such as those of endometrial cancer with fertility-sparing treatment for monitoring the disease, or those of severe intrauterine adhesion who need adhesiolysis for subsequent conception, in whom the appropriate protocol of repeatedly applying hysteroscopy lacks consensus. This article reviews the literature to find the best available evidence on the effectiveness of office hysteroscopy in comparison with other clinical diagnostic tools, as well as the current opinions on such controversies in its application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2018.12.012DOI Listing
November 2019

Use of Chinese Herbal Medicine Improves Chemotherapy-Induced Thrombocytopenia among Gynecological Cancer Patients: An Observational Study.

Evid Based Complement Alternat Med 2018 12;2018:4201325. Epub 2018 Jul 12.

Biostatistics Unit, Clinical Trial Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Background: Chemotherapy-induced thrombocytopenia (CIT) is a serious complication among patients with gynecological malignancies, yet management options are limited. This study aimed at reporting the potential of the Chang Gung platelet elevating formula (CGPEF), a prescription with a fixed proportion of Chinese herbs, for improving CIT among gynecologic cancer patients.

Materials: From 1/1/2007 to 31/12/2009, a total of 23 patients with two consecutive CIT episodes (≤ 100×10 /L) (last cycle: C0; index cycle: C1) received the CGPEF from the nadir of platelet count of C1 and through the subsequent chemotherapy cycles (C2 and beyond). The CGPEF was taken orally four times a day. The evolution of platelet counts of 18 patients after administration of CGPEF was analyzed (2 patients had different chemotherapy regimens after CGPEF, two patients discontinued CGPEF due to the flavor and the amount of CGPEF, and one patient had no further chemotherapy).

Results: Most of the patients had recurrent ovarian cancer (11/18, 61%) with a median of 2.5 previous chemotherapy regimens, and carboplatin-based regimens were the most commonly used for these patients (13/18, 72%). The trend of successive CIT could be reversed after taking CGPEF. Also, the platelet nadir was higher after CGPEF treatment (16.5×10/L versus 32×10/L, before and after CGPEF treatment, resp., = 0.002). Moreover, the chemotherapy interval decreased from 30.5 days to 24 days. No thrombocytosis, clinical bleeding, thromboembolism, or other adverse events were found among these patients.

Conclusions: The CGPEF is worthy of further large-scale, well-designed clinical trials for CIT among gynecological cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/4201325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106719PMC
July 2018

Roles of posttherapy F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy.

Eur J Nucl Med Mol Imaging 2018 07 22;45(7):1197-1204. Epub 2018 Feb 22.

Gynecologic Cancer Research Center, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan.

Purpose: To assess the clinical roles of [F]fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) performed 2-3 months after completion of concurrent chemoradiotherapy (CCRT), along with pretherapy characteristics, in patients with advanced squamous cell carcinoma of the uterine cervix enrolled in a prospective randomized clinical trial.

Methods: Posttherapy PET/CT in patients with advanced FIGO stage or positive pelvic or para-aortic lymph node (PALN) defined on pretherapy PET/CT was classified as positive, equivocal, or negative. Overall survival (OS) rates between patients with different PET/CT results are compared. Pretherapy characteristics are examined for association with posttherapy PET/CT results and for prognostic significance in patients with equivocal or negative PET/CT.

Results: PET/CT scans (n = 55) were positive, equivocal and negative in 9, 13 and 33 patients, respectively. All patients with positive scans were confirmed to have residual or metastatic disease and died despite salvage therapies. There is a significant OS difference between patients with positive and equivocal scans (P < .001) but not between patients with equivocal and negative scans (P = .411). Positive pretherapy PALN is associated with positive posttherapy PET/CT (P = .033) and predicts a poorer survival in patients with equivocal or negative posttherapy PET/CT (P < .001).

Conclusions: Positive PET/CT 2-3 months posttherapy implies treatment failure and novel therapy is necessary to improve outcomes for such patients. A more intense posttherapy surveillance may be warranted in patients with positive pretherapy PALN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-018-3957-8DOI Listing
July 2018

Comparison of positron emission tomography/computed tomography and magnetic resonance imaging for posttherapy evaluation in patients with advanced cervical cancer receiving definitive concurrent chemoradiotherapy.

Eur J Nucl Med Mol Imaging 2018 05 20;45(5):727-734. Epub 2017 Nov 20.

Gynecologic Cancer Research Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.

Purpose: Our purpose was to assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) and pelvic/abdominal magnetic resonance imaging (MRI) after concurrent chemoradiotherapy (CCRT) for posttherapy evaluation in patients with advanced cervical cancer.

Methods: Patients with cervical squamous cell carcinoma, either with advanced FIGO stage or with positive pelvic or para-aortic lymph node (PALN), received PET/CT using [F]fluorodeoxyglucose and MRI including diffusion-weighted imaging between 2 and 3 months after CCRT completion. PET/CT were interpreted independently by two nuclear medicine physicians and MRI by two radiologists using the same scoring system. Active residual tumor was proven by pathological confirmation or disease progression on imaging studies within one year after CCRT and the disease regions were classified as local, regional, PALN, or distant. Patient-based and region-based comparison was performed using the receiver operating characteristic curve analysis.

Results: The study included 55 patients and 15 (27%) patients had active residual tumor. The diagnostic performance of PET/CT is significantly superior to that of MRI in patient-based analysis (P = 0.025) and in the detection of local (P = 0.045) and regional (P = 0.014) disease. The patient-based sensitivity, specificity, and accuracy of PET/CT are 60%, 100%, and 89% while those of MRI are 27%, 100%, and 80%.

Conclusions: PET/CT is superior to MRI for posttherapy evaluation in patients with advanced cervical cancer 2-3 months after definitive CCRT, mainly for the detection of residual local and regional disease. Patients with negative or equivocal results should be followed up regularly due to suboptimal sensitivities of imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-017-3884-0DOI Listing
May 2018

Outcomes and prognoses of patients with ovarian cancer using bevacizumab: 6-year experience in a tertiary care hospital of northern Taiwan.

PLoS One 2017 3;12(5):e0175703. Epub 2017 May 3.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital. Taoyuan, Taiwan.

Purpose: Bevacizumab (BEV) has been used for ovarian cancer (OC) for years in Taiwan, but the associated data related to outcome is scant. This retrospective study reviewed patients with OC treated with BEV and analyzed their results.

Patients And Methods: All patients with OC treated with BEV from 2009 to 2015 in the Linkou branch of Chang Gung Memorial Hospital in Northern Taiwan were included. According to the means of administration, the patients were classified into 6 groups as follows: A-BEV plus chemotherapy (C/T) for initial platinum-resistant (PR) recurrent OC, B-BEV plus C/T for initial platinum-sensitive (PS) recurrent OC, C-BEV alone for recurrent OC, D-BEV plus 1st adjuvant C/T, E-BEV plus neoadjuvant C/T, and F-intraperitoneal (IP) BEV. Progression-free survival (PFS), overall survival (OS), hazard ratios (HRs), overall response rate (ORR), and mean number of BEV cycles were analyzed for groups A to E. Clinical improvement of ascites was assessed for group F.

Results: A comparison of early use (only one round of prior C/T) versus late use (multiple rounds of prior C/T) in patients of groups A and B showed a superior PFS (8.27 vs. 3.67, p = 0.037) in the early use group. No significant differences were found between groups A and B (PFS: 4.24 vs. 4.17 months, p = 0.690; OS: 10.06 vs. 9.93 months, p = 0.819; mean BEV cycles: 4.63 vs. 5.0 p = 0.992; ORR: 48.1% vs. 53.5%, p = 0.425). Comparing the response and non-response subgroups of patients in groups A and B, a better outcome was associated with endometrioid type cell (HR = 0.28, p = 0.008), good ECOG performance status (HR = 0.51, p = 0.005), and lack of ascites (HR = 0.67, p = 0.004). Comparing group C with groups A plus B, the BEV alone group had a poorer PFS (1.02 VS. 4.19, p = 0.04) and OS (1.42 VS. 9.99 p = 0.001) than the BEV plus C/T group. In group F, a good clinical benefit rate (85.6%) of ascites improvement was noted. Two patients had grade 5 gastrointestinal bleeding and venous/arterial thromboembolic events after administration of BEV. Grade 3 neutropenia and thrombocytopenia occurred more frequently in our study.

Conclusion: Early use of BEV combined with chemotherapy had a significant benefit in PFS for patients with recurrent OC. BEV plus chemotherapy was better than BEV alone for recurrent OC. In addition, IP BEV was helpful for improving clinical ascites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175703PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415172PMC
September 2017

Positron emission tomography in the management of documented or suspected recurrent ovarian cancer.

J Formos Med Assoc 2017 Nov 11;116(11):869-879. Epub 2017 Jan 11.

Department of Obstetrics and Gynaecology, Chang Gung Memorial Hospital Linkou Medical Centre, Taoyuan, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynaecologic Cancer Research Centre, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address:

Background: To prospectively evaluate the value of positron emission tomography (PET) or integrated computed tomography (CT) and PET (PET/CT) in the management of documented or suspected recurrent ovarian cancer.

Methods: Patients with ovarian cancer who had completed primary cytoreductive surgery and standard adjuvant chemotherapy were studied to evaluate the following indications: (1) CA125 elevation after complete remission with negative CT or magnetic resonance imaging (MRI) result; (2) post-therapy surveillance CT/MRI-detected suspicious lesions that guided biopsy was not feasible; (3) documented relapse for restaging prior to or after curative salvage therapy. The clinical impact of PET, as compared with those of CT/MRI, was determined on a per scan basis.

Results: From 2002 to 2009, 73 patients were recruited, and 92 PET scans were performed. Up to June 2015, 53 patients had died of disease, four were alive with disease, and the remaining 16 were alive without disease. Among the 92 scans, PET had positive impacts in 72.8%, no clinical impacts in 21.7%, and negative impacts in 5.4%. For indication 1, the sensitivity and positive predictive value of PET in detecting recurrence were 80.0% and 92.3%, respectively. For indication 2, the sensitivity, specificity, positive predictive value, and negative predictive value of PET were 91.2%, 62.5%, 91.2%, and 62.5%, respectively. For indication 3, PET provided positive impact in 85.3% and negative impact in 2.9% of the 34 scans.

Conclusion: PET has value in the management of suspected or documented recurrent ovarian cancer, with positive impacts on confirming recurrent status and offering a better treatment plan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2016.12.007DOI Listing
November 2017

Growth hormone-releasing hormone antagonist inhibits the invasiveness of human endometrial cancer cells by down-regulating twist and N-cadherin expression.

Oncotarget 2017 Jan;8(3):4410-4421

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Chang Gung University School of Medicine, Taoyuan 333, Taiwan R.O.C.

More than 25% of patients diagnosed with endometrial carcinoma have invasive primary cancer accompanied by metastases. Growth hormone-releasing hormone (GHRH) plays an important role in reproduction. Here, we examined the effect of a GHRH antagonist on the motility of endometrial cancer cells and the mechanisms of action of the antagonist in endometrial cancer. Western blotting and immunohistochemistry (IHC) were used to determine the expression of the GHRH receptor protein. The activity of Twist and N-cadherin was determined by Western blotting. Cell motility was assessed by an invasion and migration assay. GHRH receptor siRNA was applied to knockdown the GHRH receptor in endometrial cancer cells. The GHRH antagonist inhibited cell motility in a dose-dependent manner. The GHRH antagonist inhibited cell motility and suppressed the expression of Twist and N-cadherin, and the suppression was abolished by GHRH receptor siRNA pretreatment. Moreover, the inhibition of Twist and N-cadherin with Twist siRNA and N-cadherin siRNA, respectively, suppressed cell motility. Our study indicates that the GHRH antagonist inhibited the cell motility of endometrial cancer cells through the GHRH receptor via the suppression of Twist and N-cadherin. Our findings represent a new concept in the mechanism of GHRH antagonist-suppressed cell motility in endometrial cancer cells and suggest the possibility of exploring GHRH antagonists as potential therapeutics for the treatment of human endometrial cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.13877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354842PMC
January 2017

Prevalence and clinical significance of BRCA1/2 germline and somatic mutations in Taiwanese patients with ovarian cancer.

Oncotarget 2016 Dec;7(51):85529-85541

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.

Germline and somatic BRCA1/2 mutations define a subset of patients with ovarian cancer who may benefit from treatment with poly (ADP-ribose) polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 germline mutations in Taiwanese patients with ovarian cancer are scarce, with the prevalence of somatic mutations being unknown. We aim to investigate the occurrence of BRCA1/2 mutations in 99 Taiwanese patients with ovarian cancer which included serous (n = 46), endometrioid (n = 24), and clear cell (n = 29) carcinomas. BRCA1/2 mutations were identified using next-generation sequencing of formalin-fixed paraffin-embedded tumor samples. Pathogenic variants (BRCA1: n = 7; BRCA2: n = 6) were detected in 12.1% (12/99) of the study patients. Somatic and germline BRCA1/2 mutation rates in serous ovarian cancer are 4/46 (8.7%) and 8/46 (17%), respectively. All of the pathogenic BRCA1/2 mutations were identified in serous carcinoma samples (12/46; 26.1%). One-third (4/12) of the deleterious BRCA1/2 mutations occurred in tumor tissues only (somatic mutations). All of them coexisted with loss of heterozygosity, resulting in biallelic BRCA inactivation. Five novel pathogenic mutations were identified, including four somatic variants (BRCA1 p.S242fs, BRCA1 p.F989fs, BRCA1 p.G1738fs, and BRCA2 p.D1451fs) and a germline variant (BRCA2 p.E260fs). We also detected additional six novel mutations (three in BRCA1 and three in BRCA2) with pathogenic potentials. We conclude that BRCA1/2 mutations are common in Taiwanese patients with serous ovarian carcinoma and similar to mutation rates in other ethnic groups. The analysis of BRCA1/2 somatic mutations is crucial for guiding therapeutic decisions in ovarian cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.13456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356755PMC
December 2016

A preliminary investigation into textural features of intratumoral metabolic heterogeneity in (18)F-FDG PET for overall survival prognosis in patients with bulky cervical cancer treated with definitive concurrent chemoradiotherapy.

Am J Nucl Med Mol Imaging 2016 6;6(3):166-75. Epub 2016 Jul 6.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University Taoyuan, Taiwan.

We examined the role of intratumoral metabolic heterogeneity on (18)F-FDG PET during concurrent chemoradiotherapy (CCRT) in predicting survival outcomes for patients with cervical cancer. This prospective study consisted of 44 patients with bulky (≥ 4 cm) cervical cancer treated with CCRT. All patients underwent serial (18)F-FDG PET studies. Primary cervical tumor standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) were measured in pretreatment and intra-treatment (2 weeks) PET scans. Regional textural features were analyzed using the grey level run length encoding method (GLRLM) and grey-level size zone matrix. Associations between PET parameters and overall survival (OS) were tested by Kaplan-Meier analysis and Cox regression model. In univariate analysis, pretreatment grey-level nonuniformity (GLNU) > 48 by GLRLM textural analysis and intra-treatment decline of run length nonuniformity < 55% and the decline of TLG (∆TLG) < 60% were associated with significantly worse OS. In multivariate analysis, only ∆TLG was significant (P = 0.009). Combining pretreatment with intra-treatment factors, we defined the patients with a initial GLNU > 48 and a ∆TLG ≤ 60% as the high-risk group and the other patients as the low-risk. The 5-year OS rate for the high-risk group was significantly worse than that for the low-risk group (42% vs. 81%, respectively, P = 0.001). The heterogeneity of intratumoral FDG distribution and the early temporal change in TLG may be an important predictor for OS in patients with bulky cervical cancer. This gives the opportunity to adjust individualized regimens early in the treatment course.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965521PMC
August 2016

Implication of genomic characterization in synchronous endometrial and ovarian cancers of endometrioid histology.

Gynecol Oncol 2016 10 5;143(1):60-67. Epub 2016 Aug 5.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan. Electronic address:

Objectives: Synchronous endometrial and ovarian carcinomas (SEOCs) present gynecologic oncologists with a challenging diagnostic puzzle: discriminating between double primary cancers and single primary cancer with metastasis. We aimed to determine the clonal relationship between simultaneously diagnosed endometrial and ovarian carcinomas.

Methods: Fourteen pairs of SEOCs of endometrioid type and two pairs of SEOCs with disparate histologic types (control for dual primary tumors) were subjected to massively parallel sequencing (MPS) and molecular inversion probe microarrays.

Results: Thirteen of the 14 pairs of SEOCs harbored somatic mutations shared by both uterine and ovarian lesions, indicative of clonality. High degree of chromosomal instability in the tumors from 10 patients who received adjuvant chemotherapy, of whom 9 had synchronous carcinomas with significantly overlapping copy number alterations (CNAs), suggestive of single primary tumors with metastasis. The clonal relationship determined by genomic analyses did not agree with clinicopathological criteria in 11 of 14 cases. Minimal CNAs were identified in both ovarian and endometrial carcinomas in 4 patients, who did not receive adjuvant chemotherapy and experienced no recurrent diseases. In contrast, two of the 10 patients with chromosomally unstable cancers developed recurrent tumors.

Conclusion: Our findings support a recent paradigm-shifting concept that most SEOCs originate from a single tumor. It also casts doubt on the clinicopathological criteria used to distinguish between dual primary tumors and single primary tumor with metastasis. Testing of CNAs on SEOCs may help determining the need of adjuvant therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2016.07.114DOI Listing
October 2016

H MR spectroscopy in cervical carcinoma using external phase array body coil at 3.0 Tesla: Prediction of poor prognostic human papillomavirus genotypes.

J Magn Reson Imaging 2017 03 19;45(3):899-907. Epub 2016 Jul 19.

Department of Radiation Oncology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Guishan, Taoyuan, Taiwan.

Purpose: To assess the clinical value of proton ( H) MR spectroscopy in cervical carcinomas, in the prediction of poor prognostic human papillomavirus (HPV) genotypes as well as persistent disease following concurrent chemoradiotherapy (CCRT).

Materials And Methods: H MR spectroscopy using external phase array coil was performed in 52 consecutive cervical cancer patients at 3 Tesla (T). Poor prognostic HPV genotypes (alpha-7 species or absence of HPV infection) and persistent cervical carcinoma after CCRT were recorded. Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test and areas under the receiver operating characteristics curve (AUC) analysis.

Results: A 4.3-fold (P = 0.032) increased level of methyl resonance at 0.9 ppm was found in the poor prognostic HPV genotypes, mainly attributed to the presence of HPV18, with a sensitivity of 75%, a specificity of 81%, and an AUC of 0.76. Poor prognostic HPV genotypes were more frequently observed in patients with adeno-/adenosquamous carcinoma (Chi-square, P < 0.0001). In prediction of the four patients with persistent disease after CCRT, elevated methyl resonance demonstrated a sensitivity of 100%, a specificity of 74%, and an AUC of 0.82.

Conclusion: H MR spectroscopy at 3T can be used to depict the elevated lipid resonance levels in cervical carcinomas, as well as help to predict the poor prognostic HPV genotypes and persistent disease following CCRT. Further large studies with longer follow up times are warranted to validate our initial findings.

Level Of Evidence: 1 J. Magn. Reson. Imaging 2017;45:899-907.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jmri.25386DOI Listing
March 2017

Utility of (18)F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy: a parallel study of a prospective randomized trial.

Eur J Nucl Med Mol Imaging 2016 Sep 10;43(10):1812-23. Epub 2016 May 10.

Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 5, Fu-Shin St., Gueishan Township, Taoyuan County, 33305, Taiwan.

Purpose: The aim of this prospective study was to assess the usefulness of (18)F-FDG PET/CT performed before and during treatment for predicting treatment failure in patients with advanced squamous cell carcinoma of the uterine cervix treated with concurrent chemoradiotherapy (CCRT).

Methods: Patients with cervical squamous cell carcinoma, International Federation of Gynecology and Obstetrics stage III/IVA or positive pelvic or paraaortic lymph node (LN) metastasis without other distant metastasis on PET/CT entering a randomized trial of CCRT (AGOG 09-001) were eligible. PET/CT scans were performed at baseline, during week 3 of CCRT and 2 - 3 months after CCRT. PET/CT parameters were correlated with sites of failure and overall survival (OS). The resulting predictors developed from the study cohort were validated on two independent datasets using area under the curve values, sensitivities and specificities.

Results: With a median follow-up of 54 months for survivors, 20 (36 %) of the 55 eligible patients were proven to have treatment failure. Sites of failure were local in five, regional in 11, and distant in 11. Four predictors for local failure, three for regional failure, and four for distant failures were identified. After validation with two independent cohorts of 31 and 105 patients, we consider the following as clinically useful predictors: pretreatment metabolic tumour volume (MTV) and during-treatment cervical tumour MTV for local failure; during-treatment SUVnode (maximum standardized uptake value of LNs) for regional and distant failure, and during-treatment MTV for distant failure. During-treatment SUVnode (P = .001) and cervical tumour MTVratio (P = .004) were independent significant predictors of OS by stepwise Cox regression.

Conclusion: PET/CT imaging before and during treatment is useful for predicting failure sites and OS, making tailored therapeutic modifications feasible with potential outcome improvement during primary therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-016-3384-7DOI Listing
September 2016

Self-sampling HPV test in women not undergoing Pap smear for more than 5 years and factors associated with under-screening in Taiwan.

J Formos Med Assoc 2016 Dec 23;115(12):1089-1096. Epub 2015 Dec 23.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address:

Background/purpose: Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasms. A prospective population-based study was conducted investigating whether a self-sampling human papillomavirus (HPV) test was feasible for under-users of Pap smear and factors associated with under-screening in Taiwan.

Methods: Women not having Pap smear screening for > 5 years were invited to participate in this study. Invitation letters and educational brochures were mailed to 4% of randomly selected eligible women from Taoyuan City, Taiwan, and responders received an HPV self-sampling kit. Those with HPV-positive results were recalled for a Pap smear and colposcopy.

Results: Between March 2010 and June 2012, 10,693 women were invited, 354 responded (3.3%), and 282 (2.6%) gave valid informed consent, answered the questionnaire, and submitted HPV samples. The median age of enrolled women was 48.1 years. Forty-seven women (16.7%) had a positive HPV test, and 14 women accepted further survey to find two CIN2+. Another two cases of CIN2+ were identified from a national registry database. The cost of direct mailing self-samplers was less than that done on request (from NT$434,866 to NT$164,229, response rate of 5% to 15%, respectively, versus NT$683,957 for detecting 1 CIN2+). Reasons for not attending screening included lack of time, embarrassment, assumed low risk, fear of positive results, and perceived potential pain. Among the responders, 90.8% found the method acceptable.

Conclusion: Our study indicated that different approaches (e.g., direct mailing self-samplers to under-users and/or various educational interventions) must be explored to improve coverage in populations with culture characteristics similar to Taiwan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2015.10.014DOI Listing
December 2016

(18)F-FDG PET in small-cell cervical cancer: a prospective study with long-term follow-up.

Eur J Nucl Med Mol Imaging 2016 Apr 31;43(4):663-74. Epub 2015 Oct 31.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, 5 Fu-Shin St. Kueishan, Taoyuan, 333, Taiwan.

Purpose: Small-cell cervical cancer (SCCC) is rare and prone to metastasize. We conducted a prospective study to evaluate the role of (18)F-FDG PET in the management of this aggressive malignancy.

Methods: Patients with untreated primary, histologically confirmed SCCC were enrolled. (18)F-FDG PET (or PET/CT) was performed immediately after MRI or CT, for primary staging, monitoring response to treatment or restaging when there was suspicion of recurrence. The clinical impact of PET was determined on a scan basis.

Results: A total of 25 patients were recruited and 43 PET scans were performed. The PET images were obtained for primary staging (25 patients), monitoring response (10 patients) and restaging when there was suspicion of recurrence (8 patients). The median follow-up time in event-free patients was 109.3 months (range 97.5 - 157.7 months). A positive impact of PET was found in 8 (18.6 %) of the 43 scans, which included detection of additional regions of distal lymph node (LN) metastasis (one primary staging scan, two restaging scans), bone metastasis (two primary staging scans, one monitoring response scan), and exclusion of false-positive lesions on MRI (one primary staging scan, one restaging scan). On the other hand, one negative impact was recorded as one false-positive lesion on a restaging PET scan. One positive impact was noted for monitoring response (bone metastasis). The impact of three scans was indeterminate. The positive impact of down-staging in avoiding overtreatment but finding additional distal LN (except one on restaging) or bone metastases had no beneficial effect on long-term survival.

Conclusion: The results of this preliminary study suggest that PET is useful in the management of SCCC. PET could have more value in detecting occult metastases if future novel therapies are able to offer better control of extensive SCCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-015-3229-9DOI Listing
April 2016

Immunomodulatory therapy in refractory/recurrent ovarian cancer.

Taiwan J Obstet Gynecol 2015 Apr;54(2):143-9

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan. Electronic address:

Objective: To investigate the efficacy and toxicity of immunomodulatory therapy (IMT) alone or as an add-on to palliative/salvage chemotherapy in patients with refractory/recurrent epithelial ovarian cancer (EOC).

Materials And Methods: We retrospectively analyzed the efficacy and toxicity of IMT in 15 patients with refractory/recurrent EOC who had previously received multiple chemotherapy regimens.

Results: The median age of the patients was 56 years (range, 41-75 years). Three patients were platinum-sensitive, two were platinum-resistant, and the remaining 10 patients were refractory to platinum-based front-line chemotherapy. IMT consisted of picibanil (OK-432) on Day 1, interleukin-2 and/or interferon-α on Day 2 administered by subcutaneous injection (every week or 2-weekly). Five patients never received metronomic oral cyclophosphamide. After IMT, three patients achieved partial remission (PR, lasting for 11 months, ≥ 12 months, and 16 months), and six patients had stable disease (SD). The disease stabilizing rate (PR+SD) was 60% (3/3 in platinum-sensitive and 6/12 in platinum-resistant/refractory patients). The absolute lymphocyte count (ALC) at 1 month after IMT was significantly higher in the PR+SD group (median 1242.0/μL) than in the progression group (median 325.0/μL) (p = 0.012). No ≥ Grade 3 toxicities were observed. The median post-IMT survival time was 12 months (range, 2-39 months).

Conclusion: IMT alone or add-on to palliative/salvage chemotherapy for refractory/recurrent EOC achieves a substantial disease stabilizing rate without severe toxicity, which might be a potential option in selected patients. The ALC 1 month after IMT could be an early indicator to disease stabilization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tjog.2014.04.027DOI Listing
April 2015

A randomized trial comparing concurrent chemoradiotherapy with single-agent cisplatin versus cisplatin plus gemcitabine in patients with advanced cervical cancer: An Asian Gynecologic Oncology Group study.

Gynecol Oncol 2015 Jun 28;137(3):462-7. Epub 2015 Mar 28.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou and Chang Gung University College of Medicine, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address:

Objective: A recent randomized trial demonstrated that concurrent chemoradiotherapy (CCRT) with weekly cisplatin and gemcitabine, followed by two adjuvant cycles of cisplatin and gemcitabine improved survival for advanced cervical cancer patients. An Asian Gynecologic Oncology Group (AGOG) study was designed to determine whether only adding gemcitabine in the chemoradiation phase without adjuvant chemotherapy could improve survival.

Methods: Between March 2009 and March 2013, 74 eligible patients with International Federation of Obstetrics and Gynecology stage III/IVA cervical cancer or stage I/II with positive pelvic/para-aortic nodal metastasis were enrolled. Thirty-seven patients were randomized to arm C (weekly cisplatin 40mg/m(2)) and 37 patients were randomized to arm CG (weekly cisplatin 40mg/m(2) and gemcitabine 125mg/m(2)), for six cycles. Six eligible patients were excluded before the beginning of treatment.

Results: An interim analysis showed superimposable progression-free (PFS) and overall survival (OS), a decision of closing accrual was made. A 3-year PFS was similar in both arms (arm C 65.1% vs. arm CG 71.0%, p=0.71), and a 3-year OS was 74.1% in arm C vs. 85.9% in arm CG (p=0.89), but crossed over at 5years. Grade 2-4 hematological toxicities, including neutropenia (p=0.028) and thrombocytopenia (p=0.001), were more frequent in arm CG than arm C.

Conclusions: Despite limitation in power, it suggests that only adding gemcitabine at the CCRT phase does not provide substantially superior results, but treatment toxicities could increase. Further studies are required to determine the role of post-CCRT adjuvant chemotherapy in advanced cervical cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2015.03.046DOI Listing
June 2015

Social support buffers the effect of self-esteem on quality of life of early-stage cervical cancer survivors in Taiwan.

Eur J Oncol Nurs 2015 Oct 14;19(5):486-94. Epub 2015 Mar 14.

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, and College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.

Purpose: The purpose of this study was to examine the effects of self-esteem and social support on quality of life (QoL) in stage I and II cervical cancer survivors.

Method: The sample consisted of 110 participants who had been diagnosed with stage I-II cervical cancer and had completed their treatment 5 years or more before data collection. Each participant completed four structured questionnaires: a demographic-disease survey, the Rosenberg Self-Esteem Scale, Medical Outcomes Study Social Support Survey, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30. Data were analyzed using descriptive statistics, independent sample t-test, one-way ANOVA, and hierarchical multiple linear regression analyses.

Results: The participants' mean age was 60.74 ± 10.69 years. Better QoL was significantly associated with younger age, higher self-esteem, and stronger social support; in addition, social support buffered the effect of self-esteem on global QoL. Together, five variables (age, time since treatment, self-esteem, social support, and the interaction term of self-esteem and social support) explained 36% of the variance in global QoL, with self-esteem being the strongest predictor.

Conclusions: The results of this study advance current knowledge of QoL in cervical cancer survivors by demonstrating that survivors with low self-esteem and social support tend to have lower QoL than those with low self-esteem but high social support. Health professionals should help survivors seek support and provide appropriate strategies to expand their social networks and enhance their self-esteem to improve their global QoL after cervical cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejon.2015.02.008DOI Listing
October 2015

Pedicle perforator flaps for vulvar reconstruction--new generation of less invasive vulvar reconstruction with favorable results.

Gynecol Oncol 2015 Apr 14;137(1):66-72. Epub 2015 Jan 14.

Division of Reconstructive Microsurgery, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address:

Objectives: Vulvar reconstruction after cancer surgery remains challenging. Pedicle perforator flaps are believed to be a less invasive option with better cosmesis.

Methods: A retrospective review identified 27 flaps in 16 patients who underwent vulvar reconstruction after cancer surgery using island pedicled perforator flaps. Their average age was 55.7±17.8 years (Range: 22-85). The average BMI was 23.5±4.0 (range: 18.8-28.5). Five of the 16 patients underwent unilateral vulvar reconstruction, and 11 of them underwent bilateral vulvar-perineal reconstructions. The perforator flaps included deep femoral (profunda) artery perforator (DFAP or PAP) flaps (n=11), medial circumflex femoral perforator (MCFAP) flaps (n=8), external pudendal artery perforator (EPAP) flaps (n=2), medial thigh free style perforator flaps (n=2), and internal pudendal artery perforator flaps (n=4).

Results: All flaps survived with a 100% success rate. Three patients developed small wounds that required debridement and closure after the reconstruction. All donor sites were closed primarily. One patient developed temporary peroneal nerve palsy. During follow-up, none of the patients presented with donor site morbidities. All of the patients were satisfied with the cosmetic and functional results, except that one patient underwent a flap debulking procedure three months after surgery.

Conclusions: Compared to traditional myocutaneous flaps, perforator flaps provide thinner fasciocutaneous flaps for vulvar reconstruction with favorable reconstruction results and fewer donor site morbidities. The medial or inner thigh is a region that is rich in perforators, which allow for more versatile flap design according to the defect. Furthermore, most of the donor site can be closed primarily without complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2015.01.526DOI Listing
April 2015

Serum microRNAs in clear cell carcinoma of the ovary.

Taiwan J Obstet Gynecol 2014 Dec;53(4):536-41

Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Gynecologic Cancer Research Centre, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address:

Objective: To identify candidate microRNAs (miRNAs) in the serum of patients with clear cell carcinomas in monitoring disease progression.

Materials And Methods: The sera of patients with diagnosed ovarian clear cell carcinoma were collected from 2009 to 2012. Real-time quantitative polymerase chain reaction (PCR) analysis for 270 miRNAs was performed. To offset the potential extraction bias, an equal amount of Caenorhabditis elegans cel-miR-238 was added to each serum specimen before miRNA isolation. miRNA expression was analyzed using the ΔCt method, with cel-miR-238 as controls.

Results: Twenty-one patients with clear cell carcinoma were included. In the discovery phase on four pairs of pre- and postoperative sera, 18 differentially expressed miRNAs were selected from 270 miRNAs. In the validation phase on an independent set of 11 pairs of pre- and postoperative sera, 4 miRNAs (hsa-miR-130a, hsa-miR-138, hsa-miR-187, and hsa-miR-202) were confirmed to be higher in the preoperative sera. In the application phase, hsa-miR-130a remained consistent with the different time points in seven of the 10 patients during clinical follow-up periods. More importantly, in three patients, hsa-miR-130a levels were elevated in early disease recurrences before CA125 was found to be elevated.

Conclusion: Hsa-miR-130a may be a useful serum biomarker for detecting recurrence of ovarian clear cell cancer, and warrants further studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tjog.2014.07.005DOI Listing
December 2014